Hepatitis type B virus (HBV) is a pathogen of considerable interest to the medical community. An etiological agent in acute and chronic hepatitis and liver cirrhosis, this virus has also been linked to hepatocellular carcinoma. In certain areas of the world such as Central Africa and East Asia, as many as ten percent of the population carry HBV, and a large percentage of these individuals die from its effects.
Investigations into the replication, expression and other aspects of the life cycle of HBV in an effort to develop antiviral drugs and immunological agents, have been hampered, in part, by the elusiveness of a suitable stable cell line for in vitro propagation of infectious virus. Numerous investigators, such as Yaginuma et al., Proc. Natl. Acad. Sci. USA, 84: 2678-2682 (1987) and Chang et al., EMBO J., 6(3): 675-680 (1987) tried, but were unable, to establish stable culture systems using relatively differentiated human hepatocellular carcinoma cell line HuH-7. A few select investigators did eventually report success using the relatively differentiated human hepatoma cell lines Huh6-c15 and HepG2. See Tsurimoto et al., Proc. Natl. Acad. Sci. USA, 84: 444-448 (1987), Sureau et al., Cell, 47: 37-47 (1986) and Sells et al., Proc. Acad. Sci. USA, 84: 1005-1009 (1987). To date, however, no successful efforts have been reported in which a nonhuman cell line of any differentiated state has been stably transfected in vitro with human HBV genome. See Zelent et al., J. of Virol., 61: 2921-2923 (1987) and Seifer et al., "1987 Meetings on Hepatitis B Viruses," pp. 11, Cold Spring Harbor Laboratory (N.Y., 1987). Additional stable in vitro systems, including nonhuman systems, are needed. Cell lines capable of efficient expression and secretion of the gene products of hepatotropic viruses such as human HBV would also be useful. The present invention is directed to these ends.